1,3-Thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4-yl) butanoyl]amino}-1,6-diphenylhexan-2-yl]carbamate having the structural formula-1 is Cytochrome P450 monooxygenase inhibitors and also known as Cobicistat. The compound of formula-1 of the present invention is used in the treatment of human immunodeficiency virus (HIV). Cobicistat is a component of a four-drug, fixed-dose combination for HIV treatment Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (known as the “Quad Pill” or Stribild®). The Quad Pill/Stribild was approved by the FDA in August 2012 for use in the United States. This is also approved in US under the brand name of TYBOST®.
Cobicistat is a potent inhibitor of cytochrome P450 3A enzymes, including the important CYP3A4 subtype. It also inhibits intestinal transport proteins, increasing the overall absorption of several HIV medications, including atazanavir, darunavir, and tenofovir alafenamide fumarate.
Various synthetic routes are available for the synthesis of the compound of formula-1. U.S. Pat. No. 8,148,374 first disclosed the compound of formula-1 and process for its preparation. The compound of formula-1 is a straight chain having three peptide bonds. US '374 disclose some possibilities to preparation of the compound of formula-1.

The disclosed process involves the usage of strong basic agents leading to lower yields and less purity due to the formation of byproducts.
Cobicistat (Tybost, and component of Stribild, Gilead) is a novel cytochrome P450 (CYP) enzyme (CYP3A4) inhibitor used as a “booster” in combination with some HIV treatments, e.g. protease inhibitors, to reduce their metabolism during absorption and so increase the amount of unchanged drug reaching the systemic circulation. Ritonavir is also used as such a boosting agent but cobicistat differs in that it has no anti-viral activity of its own and is purely used to modify pharmacokinetics.
Cobicistat drug substance does not occur in crystalline form and is isolated as amorphous, hygroscopic solid foam of low glass transition temperature which readily transforms under ambient conditions via a moisture and temperature-driven phase transformation into a rubber-like material that is difficult to process into dosage forms. The removal of the absorbed moisture and reversion to the original solid form does not occur.
International patent publication number WO 2009/135179 A1 discusses the difficulties associated with processing the compound of formula-1 and describes combining the compound of formula-1 with solid carrier particles such as silicon-dioxide to improve the physical properties of the resulting solid material. But the silicon-dioxide carrier particles contribute to the overall weight and volume of the solid so that significantly more material is required in a formulation to achieve a given dose of the compound of formula-1. Accordingly, there is a need for solid forms of the compound of formula-1 that have the beneficial properties of the solids described in WO2009/135179 A1 but lack the inert carrier particles that contribute to the weight and the volume of the solid.
By adsorbing onto silica by evaporation from dichloromethane solution of drug as part of the isolation of the cobicistat, a free flowing powder is produced.
The finished dosage form using the adsorbate showed bio-equivalence for cobicistat with dosage forms prepared by the ethanol/water high shear granulation process. For cobicistat, formulation technology has dealt with challenging physical properties of an active pharmaceutical ingredient and provided an approach to improved handling and manufacturing of dosage forms.
Several methods to improve the dissolution characteristics of compounds have been reported, including particle size reduction, formation of solvates, complexes and micro spheres. Additionally, attempts have been made to improve bio-availability provided by solid dosage forms by forming solid dispersions of drugs. Solid dispersions create a mixture of a poorly water soluble drug and highly soluble carriers. Solid dispersions may increase bio-availability by decreasing the energy required for solubilizing the drug and increasing the stability of the drug in solution. Traditionally these methods carry inherent limitations concerning physical stabilities of the solid dispersion on storage, problems with grinding or difficulty of removal of the solvent. Furthermore, it is important that the drug released from the solid phase does not precipitate in the small intestine tract but remains water-soluble in the aqueous fluids of the small intestine tract, since such precipitation results in low bio-availability.
The present invention provides solid dispersions having more stability and greater bioequivalence.
The present inventors have developed a novel processes for the preparation of the compound of formula-1 it has many advantages; like using simple and mild bases such as alkali metal salts avoiding pyrophoric bases making it conducive for large scale production at an industrial level; Lesser reaction times; Avoiding column chromatography technique for the purification. It also avoids the formation by-products and unwanted isomers especially in the final product, improving the yield and quality. Formation of N-oxide impurity is inhibiting by the usage of antioxidant in the reaction.